<div style="text-align: justified;"> <font face="Arial" size="2">Strong and weak hydrogen bonds in the crystal structure of the anti-cancer drug erlotinib in the kinase domain of EGFR</font><font size="2">&nbsp;</font></div><br>

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and weak hydrogen bonds in the crystal structure of the anti-cancer

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drug erlotinib in the kinase domain of EGFR</font><font size="2">&nbsp;</font></div>

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http://www.uohyd.ernet.in/

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http://www.uohyd.ernet.in/ &nbsp;&nbsp;

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<p align="left"> <font face="Arial" size="2">

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last updated 10th july 2006

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last updated 10th July 2006 <br>

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by Tejender thakur

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by Tejender thakur <br>

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email: tejenderthakur@gmail.com

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email: tejenderthakur@gmail.com <br>

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web address: http://tejenderthakur.googlepages.com

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web address: http://tejenderthakur.googlepages.com <br>

Revision as of 04:36, 10 July 2006

Drug
Design and Discovery

Computational
Approaches from X-ray Crystallography

Intermolecular interactions, especially hydrogen bonds, manifest
themselves in somewhat similar ways both in crystals of small organic
molecules and large biological macromolecules. We are trying to analyse
crystal structures of biological macromolecules with respect to
intermolecular interactions and to establish some general principles
for their assembly using ideas and concepts of crystal engineering. The
possible application of such a study is in the field of drug design.
Where drug design is concerned, an overall knowledge is vital to obtain
safer drugs. Especially, with the current importance of virtual
screening, there is an urgent need to develop methods to efficiently
study the chemical space of drug molecules. Our research aims at
understanding the overall chemical nature of drug molecules through the
study of databases of small molecules (drugs and non-drugs). In this
respect there is a continuing effort in our group to develop methods
for analysing drug-like and non-drug molecules.

Traditionally drug
design has relied more on serendipity than on rational design,
especially in the early stages of lead molecule identification. But
recent developments in the field of genomics and proteomics have forced
the researcher to adopt more rational approaches to drug design to
convert the huge amount of raw data into medicinally important
information. We follow a dual strategy using both analog and structure
based drug design based on the type of information available. In the
analog based approach we use 3D-QSAR, pharmacophore generation and de
novo design methods. On the other hand the structure based methods
include molecular docking and molecular dynamics simulations to
understand the basic nature of drug-receptor interactions. When the
target structure is not known we try to model it through a
computational approach (see illustration)
Rational drug design with a flavour of strong and weak intermolecular interactions is being applied to design novel inhibitors targeting diseases like
tuberculosis and cancer.